Mercury derivatives of propyl-hydantoins



United States Patent Ofiice 3 ,285,928 Patented Nov. 15, 1966 3,285,928 MERQURY DEREVATHVES F PROPYL- HYDANTOINS Franklyn W. Gubitz, Nassau, N.Y., assignor to Sterling Drug The, New York, N.Y., a corporation of Delaware No Drawing. Filed Aug. 23, 1965, Ser. No. 481,913 11 Claims. (Cl. 260-499) The instant application is a continuation-in-part of my copending application Serial No. 106,483, filed May 1,

1961, and now abandoned.

This invention relates to compositions of matter classified in the art of chemistry as mercurated propylhydantoins.

The invention sought to be patented, in its composition aspect, is described as residing in the concept of a chemical compound having a molecular structure in which there is attached, to the propyl group of a propylhydantoin in either the 1-, 3-, or -position of the hydantoin ring, a mercury atom bearing an anion in the 3-position, and, an oxy-functional group in the 2-position, thereby to form a 1-, 3-, or 5-(3-mercuri-2-oxypropyl)hydantoin. The compounds of this invention thus all possess a 3-mercuri-2- oxypropylhydantoin nucleus wherein a divalent mercury atom links an anion to the terminal carbon atom of an oxypropyl group and the remaining oxy valence is satisfied by a monovalent organic radical.

The tangible embodiments of the invention possess the inherent applied use characteristics of exerting a diuretic elfect in animals, as determined by standard animal evaluation procedures. Extensive pharmacological evaluation of the compounds of the invention has shown that they are valuable diuretics. Administered orally to dogs at non-toxic dose levels, the compounds produced out standing diuretic and chloruretic effects; their utility is thus indicated in the treatment of edematous conditions. Also, they are useful as intermediates for the preparation of diuretically-active compounds, as discussed more fully hereinafter.

Tangible embodiments of the inventive concept can be represented by Formula I OY wherein one of the free valences at either the 1-, 3-, or 5- position of the hydantoin ring is satisfied by the 3-mercuri- 2-oxypropyl grouping --CH rCHOI-I Hg-Anion and the remaining free valences, at either the 1-, 3-, or 5- position, are satisfied by the radicals R R and R which can be the same or different, and are hydrogen or any monovalent organic radical, among which, for purposes of illustration, can be lower-alkyl, monocyclic-aryl-loweralkyl, mono-cyclicaryl, or monocyclic aralkyl.

A preferred class, because of their easy accessibility, of the groups R R and R comprises hydrogen; loweralkyl; and, benzyl or phenyl, substituted by from 0 to 3 halo, lower-alkyl, or alkoxy groups. Representative examples of the preferred class of the groups R R and R include hydrogen, methyl, ethyl, propyl, phenyl, p-chlorophenyl, p-bromophenyl, p-fluorophenyl, 3,4-dichlorophenyl, p-tolyl, p-methoxy-phenyl, and 2,4,5-trimethylphenyl.

As used herein, the term lowenalkyl means straightor branched-chain alkyl of from one to four carbon atoms, for example, methyl, ethyl, propyl, isopropyl, isobutyl and are not vitiated by n-butyl. The term "monocyclic-aryl lower-alkyl" means lower-alkyl as defined hereinabove, and monocyclicaryl means an aromatic carbocyclic or heterocyclic radical containing no more than six atoms in the aromatic ring and carrying from zero to three substituents, for example, lower-alkyl, halogen, nitro, carbalkoxy, alkoxy, alkylmercapto, tri-fluoromethyl, and lower-alkylsulfonyl. Examples of monocyclic-aryls are: phenyl, pyridyl, thienyl, furyl, o-tolyl, p-anisyl, 2,4-di nitrophenyl, p-chlorophenyl, and S-methyl-Z-pyridyl. The term monocyclic-aralkyl means monocyclicaryl as defined hereinabove chemically bonded through an alkylene group containing from one to four carbon atoms. As used herein, the term oxy refers to the divalent O radical.

As used herein, Y means hydrogen or the organic portion of an alcoholic hydroxylic solvent, YOH, preferably containing from one to six carbon atoms, for example, methanol, ethanol, l-propanol, 2-propan-ol, l-butanol, Z-methyl-l-propanol, Z-butanol, 2-methyl-2-propanol, 1- pentanol, 3-methyl-l-butanol, 2-methyl-2-butanol, 2-pentanol, 3-pentanol, Z-methoxyethanol, ethylene glycol, 2- ethoxy-ethanol, glycerol, ethylenechlorohydrin, and ethylenebromohydrin. Y means methyl, ethyl, propyl, isopropyl, butyl, methoxyethyl, hydroxyethyl, ethoxyethyl, 2,3-dihydroxypropyl, 2-chloroethyl, Z-bromoethyl, and so forth. Any alcoholic hydroxylic solvent, containing from one to six carbon atoms, substituted or unsubstituted, is suitable so long as it reacts across the double bond of the allyl group as shown herein. The type of substituents present in the alcoholic hydroxylic solvent are immaterial so long as they do not adversely affect the addition of the OY group across the double bond. The olefinic double bond of the allyl group under the conditions of the process of this invention reacts with water to add a hydroxyl group across the double bond, or with the alcoholic hydroxylic solvent to add the corresponding ether group across the double bond. In the presence of mercury salts and a small quantity of concentrated nitric acid, as shown herein in the examples, this addition is even more pronounced.

As used herein, the term Anion means any monovalent ion derived from an organic or inorganic acid, HAnion, by the removal of an acidic hydrogen ion. Exemplary anions are, halide, hydroxy, alkanoate, nitrate, alkylsulfonate, arylsulfonate, alkylmercapto, arylmercapto, aryloxy, theophyllinyl, and succinimido. Other monovalent anions are found in the literature for example, Hackhs Chemical Dictionary, 3rd Edition (1946), at pages 12-13, and Chemical Abstracts, vol. 56, Nomenclature," at pages 72n80n, both incorporated herein by specific reference thereto.

The acids, HAnion, from which the anions are derived, are preferably those acids which produce, when combined as shown herein, medicinally acceptable salts, that is, salts whose anions are relatively innocuous to the animal organism in medicinaldoses of the salts, so that the beneficial physiological or desired diuretic properties side effects ascribable to the anions. Although ph-armaceutically acceptable salts are preferred, all salts having any anion whatsoever are useful as sources for salts having beneficial physiological or diuretic effects even if the particular salt per se is derived only as an intermediate product as, for example, when the salt is formed only for purposes of purification or identification, or when it is used as an intermediate in preparing a medicinally acceptable salt by ion exchange procedures. Therefore, the term anion includes all anions without .regard to whether or not all anions could be used with animal or negate the activity of the compound, if taken internally, can always be used as an intermediate to make other compounds within the scope of the disclosure and claims having anions which are not deleterious. Therefore, the compounds of this invention are useful as either diuretics or diuretic intermediates. The anion is merely an anion which satisfies the valence requirement of the mercuric ion. As a class, the most desirable anions are those which give rise to physiologically acceptable diuretic compounds. The most desirable anions are, of course, the physiologically acceptable anions, physiologically compatible anions, or mutually compatible anions, but the scope of the compounds herein described and claimed is in no way to be thereto restricted.

The starting materials for the 1-, 3-, or 5-(3-mercuri- 2-oxypropyl) hydantoins represented by Formula I have the following general formulae:

where R R and R have the meanings given above.

The above allylhydantoin starting material can be conveniently prepared by the acid-catalyzed cyclization of the proper hydantoic acid; thus, l-allylhydantoins of the Formula 1111 above are prepared from 3-allylhydantoic acids as in Formula IIIa:

Similarly, 3-allylhydantoins of Formula IIb above can be prepared from S-allylhydantoic acids (Formula 11117),

H R R4 (3H2=oII-oH1I IiiN o o 0 01-1 and the 2-allylhydantoic acids of Formula IIIc yield 5- allylhydantoins on cyclization.

CH =OH-CHzCR -OOOH I IR IINR;

The process for carrying out the cyclization involves heating the allylhydantoic acid in dilute or concentrated mineral acid at temperatures ranging from about 50 C. to about 150 C.

The 3 allylhydan-toins of Formula II!) can also be prepared in good yield by alkylating the appropriate hydantoin, unsubstituted in the 3-position, with an allyl halide in the presence of an acid acceptor.

1- and i-allylhydantoins which are unsubstituted in the 3-position can be alkyl-ated in that position with for example an alkyl halide or sulfate in the presence of an acid acceptor.

The alkylation or allylation of the hydantoin ring is carried out by heating the hydantoin with the 'alkylating 0r allylating agent in a suitable solvent, for example a lower-alkanol or a lower alkyl ketone. Although the reaction will proceed slowly at room temperature, it is convenient to carry out the reaction at the boiling point of the solvent selected. The acid acceptor, which is also present in the reaction medium, is a basic substance, for example, alkali-metal hydroxides or alkoxides, alkalimetal carbonates, tertiary-amines, alkali-metal amides and the like, the purpose of which is to take up the hydrogen halide or hydrogen sulfate which is formed during the course of the reaction. The acid acceptor preferably form-s a by-product which is easily separable from the rest of the reaction mixture.

The 1-, 3-, or 5-(3-mercuri-2-oxypropyl) hydantoins are conveniently prepared by reacting a mercuric salt, preferably mercuric acetate, with the appropriate allylhydantoins selected from the group shown in Formulas Ha, b and c. The reaction is carried out at temperatures ranging from 15 C. to about C. in a suitable hydroxylic solvent, as noted hereinbefore, for example, water, methanol, ethanol, n-propanol, isopropyl alcohol, n-butano'l, ethylene glycol; and monoethers of ethylene glycol. The reaction takes place at room temperature, but it is convenient to warm the mixture initially to facilitate dissolving the mercuric salt and the allylhydantoin.

The 1-, 3-, or 5-(3-mercuri-2-oxypropyl) hydantoins formed by the reaction correspond to the following forwherein Y, R R R and the Anion are as described hereinabove with reference to Formula I.

When mercuric acetate is the mercurating agent, the anion of the product first formed is acetoxy. The product wherein the anion is hydroxyl can be prepared by treating the acetoxy compound with an aqueous solution of an alkali metal hydroxide. The compounds wherein the anion is hydroxyl can then be treated with any desired acid, HAnion, to produce the corresponding compound bearing the desired anion.

Alternatively, when solubility-product relationships are favorable, a mercurial bearing a desired anion may be obtained by a simple metat-hetical reaction of the acetoxymercuri compound with a salt of the desired anion. For example, 1-(3-acetoxymercuri-Z-methoxypropyl) hydantoin, when treated with a solution of sodium chloride, give-s 1 (3-chloromercuri-Z-rnethoxypropyl) hydantoin and sodium acetate.

The best mode contemplated by the inventor of carrying out the invention will now be set forth as follows:

PREPARATION OF STARTING MATERIALS Preparation A.3-allylhydan*t0ic acid N-allylglycine (9.4 g., 0.08 mole) was dissolved in a solution containing 8.2 g. (0.1 mole) of potassium cyanate in 25 ml. of water. Upon acidification of the solution,

9.3 g. of crude product were precipitated. One recrystallization from isopropyl alcohol yielded 5.3 g. (41% of tion with ether. The residue left on evaporation of the 75 deposited 9.8 g. of white needles which,fafte on I 6 theoretical) of white prisms, M.P. 105-110 C. (dec.) ether was distilled at 77-78 C. at 0.1 mm. of Hg to (corr.). give a yellow oil which on redistillation boiled at 71-73 AnaZysis.-Calcd. for C H N O N, 17.7; NE, 158. C. at 0.08 mm. of Hg. The yield of 1-allyl-3-methylhy- Found: N, 17.8; N.E., 161. dantoin as a colorless oi-l n 1.4970, was 12.9 g.

Preparation B. 1 allylhydant0in Analysis.-Calcd. for C H N O C, 54.53; H, 6.54;

N, 18.17. Found: C, 54.74; H, 6.42; N, 18.11.

[Formula Ha; RI=R2=R3=H1 Preparation G.5-allyl3-methylhyaant0in Ethyl N-allylglycinate (48.3 g., 0.337 mole) and nitrourea (36.8 g., 0.34 mole) were dissolved in 300 ml. of [Formula R1=R2=H R3:CH3] ethanol and allowed to stand overnight at room tempera- Following the procedure outlined above for the preparature. The solution was then warmed and evaporated to tion of 1-al'lyl-3 methylhydantoin, there was obtained dryness. To the residue which was ethyl 3-allylhydantofrom 14.0 g. (0.1 mole) of 5-allylhydantoin, 28.4 g. (0.2 ate was added 75 ml. of 25% hydrochloric acid, and the mole) of methyl iodide, 27.6 g. (0.2 mole) of calcined solution Was heated on a steam bath for two hours. potassium carbonate and 250 rnlof acetone a yield, after After removing the water and excess hydrochloric acid recrystallization from ether, of 11.0 g. of 5-allyl-3-methylin vacuo, the dried yellow residue was recrystallized from hydantoin as white needles, M.P. 9092 C. (corr.). n-butanol. The crude yield of product melting at 91- Analysis.-Calcd. tor C H N O C, 54.53; H, 6.54; 96 C. (uncorn), was 41 g. Further recrystallization N,18 17, Found: C, 54.23;H, 6.55;N, 18.11. from n-butanol yielded l-allylhydantoin in the form of Following the procedures outlined above there can be blade-shaped crystals, M.P. 94.698.4 C. (C IL). prepared other allylhydantoins substituted in the 1-, 3-

Analysis--calcdfor e s z z and 5 positions by alkyl groups containing between one Follndl 9; N, 19.75. and four carbon atoms in the alkyl chain and by mono- Preparation Lallylhydantion, can also be P p cyclic-aryl lower-alkyl groups which can be substituted y the following Procedure: Suspend 'gin the aryl nucelus by up to three substituents. Exemplary mole) of 3-al1ylhydantoic acid (preparation given above) f such -u rlh i are in 50 ml. of concentrated hydrochloric acid and heat at 1 11 I 3 b 1h d t about 90 C. for 1.5 hours. Remove the water from 'g l the solution and recrystallize the dry residue from nmy amom butanol. The product crystallizes in the form of clusters l'anylls 5'mmethy1hydantom. of colorless blades. The melting point is given above. 30 Lam/1'3 '(4'chlorobenzifl) 'dlmethylhydantom 3-allyl- 1 apropylhydantorn, Preparation D.3-allyl-5 ,5 -dimethylhydanloin 11 1 1 1 5 5 1 [Formula Rl=H; R2=RS=CH31 3-allyl-5-ethylhydanto1n, 3-allyl-5-(4-chlorophenyl)hydant-orn, A solutlon of sodium methoxrde in methanol was pre- Siam/L1 3 dimethylhydantoin pared by adding 4.6 g. (0.2 mole) of sodium portionwise 5 a.11y1 3EdiethYlhYdamoin to 500 ml. of absolute methanol. Commercial 5,5-di- 5 a.ny1 3ibenzyLLmethylhyaamoin and methylhydantoin (25.6 g., 0.2 mole) was added with stir- 5 aHy1 l methylhydantoin ring, and 25.4 g. (0.21 mole) of allyl bromide was then added rather rapidly. The mixture was refluxed for 5.6 40 PREPARATION OF FINAL PRODUCTS hours, and the solvent was stripped ofl in vacuo. After Example 1.--1-(3-chloromercari-Z-methoxypropyl) extracting the product with etherand evaporating the h danto'n solvent, the oily residue was crystallized from ethery l pentane. Repeated recrystallization from the same sol- [Formula 1= z=R =H; Y=CH .Amon=Cl] ver}1; coupt1e6g1;1ggd4-g-( Willie blade-Shaped Crystals A solution containing 4.2 g. (0.3 mole) of l-allylme inga corr.

hydantoin in 100 ml. of methanol was mixed with 9.6 g. (0.03 mole) of mercuric acetate in ml of hot methanol, and the resulting solution. was treated Analysis.-Calcd. for C H N O C, 57.12; H, 7.19; N, 16.66. Found: C, 57.08; H, 7.41; N, 16.60.

Prgparwtign E, 3-allyl-1-mgfhylhydant i with two drops of concentrated nitric acid. On

v 50 standing at 25, solid 1-(3-acetoxymercuri-Z-methoxy- [Formula R2 R3 H] propyl)hydantoin precipitated. An additional 50 ml. of Following the procedure outlined above for the preparamethanol was added to dissolve the precipitate. The adtion of 3-allyl5,S-dimethylhydanto-in, there was obtained dition of a solution containing 3 g. of sodium chloride from 51 g. (0.5 mole) of 1-methylhydantoin 72.6g. (0.6 in 10 ml. of water to the methanolic solution caused the mole) of allyl bromide, and 35 g. (0.65 mole) sodium 5 precipitation of the 1-(3-chloromercuri 2 methoxymethoxide in 500 ml. of absolute methanol a yield of 35.5 propyDhydantoin which was collected and recrystallized g. of 3-allyl-l-methylhydantoin as a colorless oil boiling in once from water. The product thus obtained weighed the range of 68.71 C. (0.08 mm). An analytical sample 11.8 g. (96 percent of theory) and melted at 154.4157.6

of the compound prepared according to this procedure C. (corr.) with decomposition. was redistilled; B.P. 73-76 C. at 0.13 mm. of Hg. 0 Analysis-Calcd. for C H ClI-IgN O C, 20.64; H, Analysis.Calcd. for C H NgO C, 54.53; H, 6.54; N, Found: C, 20.99; N, 18.17. Found: C, 54.56; H, 6.66; N, 18.03. 6.82; H-g, 49.50.

Preparation F.-I-allyl-3-methylhydantoin Example 2.---5-(3-chloromercuri-Z-methoxypropyl) [Formula Ha; R =CH R =R =H] hydanlom Calcined potassium carbonate (27.6 g., 0.2 mole) was [Formula Ive; R1=R2=R3=H; Y=CH3; ground to a powder and suspended in a solution contain- Following the procedure outlined in Example 1 above, ing 14.0 g. (0.1 rnole) of l-allylhydantoin (preparation there Was obtained from 4.2 g. (0.03 mole) of 5-allyl given above) in 500 ml. of dry acetone. After the mixhydantoin, and 9.6 g. (0.03 mole) of mercuric acetate, ture had been refluxed for 1 hour, 28.4 g. (0.2 mole) of in 300 ml. of methanol a white, chalky precipitatecon} methyl iodide was added, and refluxing was continued sisting of 5 (1-acetoxymercuri 2 methoxypropyhh for 12 hours. The mixture was filtered, and the filtrate dantoin. The precipitate was dissolved in dilute acetic was concentrate-d in vacuo to a yellow oil. The crude acid and treated with 3.5 g. (0.06 mole) of sod pnoduct was separated from the inorganic salts by extracchloride in 50 ml. of water. 0n cooling, the solu 7 stillizat'ion from 100 ml. of 1:1 dimethylformamide and Water yielded 8.7 g. of -(3-chloromercuri-Z-anethoxypropyl)hydant-oin, M.P. 165.2166.2 C. (corr.) (dec) Analysis.-Calcd. for C I-I ClHgN O C, 20.64; H, 2.72; N, 6.88; Hg, 49.26. Found: C, 20.57; H, 2.71; N, 6.90; Hg, 48.3.

Example 3.-3-(3-chloromercuri-Z-methoxypropyl) hydantoin Following the procedure given in Example 1 above,

there was prepared from 5.6 g. (0.04 mole) of 3-al lylhydantoin and 12.8 g. (0.04 mole) of mercuric acetate in 200 ml. of methanol a solution of 3-(1-acetoxymercuri-2- methylpropy-l)hydantoin. A test for mercuric ion using 2 N sodium hydroxide solution indicated that methoxymercur-ation was complete in a few minutes. A solution containing 4.6 g. (0.08 mole) of sodium chloride was added, and the resulting solution was concentrated to onehalf its volume by warming on a steam bath. On cooling 3-(3-ch loromercuri-Z-methoxypropyl)hydantoin separated, and after recrystallization from water, the white prismatic crystals melted at 144.2146.0 C. (corr.).

Analysis.-Calcd. for C H ClHgN O C, 20.64; H, 2.72; Hg, 49.26. Found: C, 20.48; H, 3.42; Hg, 49.00.

Example 4 .-3 (3 -chl oromercuri-Z-methoxy pro pyl S-S-dimethylhydantoin Following the procedure given in Example 1 there was obtained from 0.03 mole of each 3-allyl-5,5'-dimethylhydantoin and mercuric acetate in 100 ml. of methanol a solution of 3-(3-acetoxymercuri-Z-methoxypropyl)-5,5-dimethylhydantoin. Following treatment with sodium chloride solution an oil was obtained which was crystallized from ethyl acetate. The product, 3-(3-chloromercuri-2- methoxypropyl)-5,5-dimethylhydantoin, was collected as white microprisms, M.P. 1 14.0-116.2 C. (corr.).

Analysis.Calcd. for C H ClHgN O N, 6.44; Hg, 46.08. Found: N, 6.42; Hg, 45.50.

Example 5.5(3-chl0r0mercuri-2-methoxypropyl) 3-methylhydant0in Following the procedure shown in Example 1, 3.5 g. (0.023 mole) of 5-allyl-3-methylhydantoin was mercurated with 4.6 g. (0.023 mole) of mercuric acetate in 150 ml. of methanol. The clear solution of 5-(3-acetoxymercuri-2-methoxypropyl)-3-methylhydantoin which resulted was treated with a solution of 5.8 g. (0.1 mole) of sodium chloride in 25 ml. of water, and 5-(3-chloromercuri-Z-methoxypropyl)-3-methylhydantoin crystallized as white needles. After recrystallization from aqueous methanol the product melted at 142.4153.6 C. (corr.)

AnaZysis.-Calcd. for C H ClHgN O C, 22.81; H, 3.11; Hg, 47.62; N, 6.65. Found: C, 22.60; H, 3.18; Hg, 46.40; N, 6.48.

Example 6 .I (3-chl0r0mercuri-2-meth0xy pro pyl 3 -methy lhydantoin Analysis.Calcd. for C H ClHgN O C, 22.81; H, 3.11; Hg, 47.62. Found: C, 23.15; H, 3.01; Hg, 46.90.

Example 7.3-(3-chloromercuri-Z-meth0xypr0pyl)- l-methylhydantoin [Formula IVb; Y=R =CH R =R =H; Anion=Cl].

Using the procedure outlined in Example 1, 3-(3-acetoxymercuri 2 methoxypropyl)-1-methy1hydantoin was obtained from 7.7 g. (0.05 mole) of 3-allyl-1-methylhydantoin, 10.0 g. (0.05 mole) of mercuric acetate, and 75 ml. of methanol. Addition of 5.8 g. (0.1 mole) of sodium chloride in 25 ml. of water to the methanolic solution and removal of the solvent produced a colorless oil. Chromatographing the oil twice on silica gel, eluting with 1:99 acetone-ether, and recrystallizing from absolute alcohol gave 3 (3 chloromercuri 2-methoxypropyl)- 1- methylhydantoin as white needles, M.P. 85.8-86.8 C. (corr.).

Analysis.-Calcd. for C H ClHgN O C, 22.81; H, 3.11; Hg, 47.62; N, 6.65. Found: C, 22.88; H, 2.86; Hg, 47.70; N, 6.55.

The procedures given in the above examples can be used to prepare many mercuripropylhydantoins of Formulas Illa, 11111, and I110. The table below shows further examples encompassed in the concept of the invention. These examples serve to illustrate the scope of the invention, and are not intended to limit it thereto. The group Y is determined by the mercuration-reaction solvent. The anion can be chosen at will under favorable solubility product conditions by a metathetical reaction of the acetoxymercuri compound, or it may be chosen by reaction of the hydroxymercuri compound with the appropriate acid, H Anion.

Depending upon the position of the substituted propyl substituent on the hydantoin ring, other positions on the hydantoin ring are available for further substitution with substituents without qualitatively affecting the pharmacological elfectiveness of the subject matter of this invention. Such other position substituted compounds are, therefore, the full equivalents of the subject matter herein described and claimed.

The subject matter which applicant regards as his invention is particularly pointed out and distinctly claimed as follows:

1. A 3 mercuri 2 oxypropyl hydantoin compound wherein a divalent mercury atom links a pharmaceutically acceptable anion to the terminal carbon atom of an oxypropyl group and the remaining oxy valence is satisfied by an alkyl, hydroxyalkyl, or haloalkyl group containing from one to six carbon atoms and any substituents present on the hydantoin nucleus are selected from the group 10. 5 (3 chloromercuri-Z-methoxypropyl)-3-methylconsisting of lower-alkyl, monocyclic-aryl-lower-alkyl, hydantoin. monocyclicaryl, or mono cyclic aralky-l.

11. 3 (3 chloromercuri 2 methoxypropyl)-5,5-di- 2. A 1-(3-haIomercuri-2-a1koxypropyl)hydantoin. methyl-hydantoin. 3. A 3-(3-halomercuri-2-alkoxypropyl)hydantoin. 5 I 4. A 5-(3-ha1omercuri-Z-alkoxypropyl)hydantoin. References Cited y the Examine! YP PY y Burger: Medicinal Chemistry, (New York, 1960), 6. 3-(3-chloromercuri-Z-methoxypropyl)hydantoin. pages 6424 and 41 5 0 B8. 7. 5-(3-ch1oromercuri-Z-methoxypropyl)hydantoin. 8. 1 (3-ch1oromercuri-Z-methoxypropyl)-3-methy1-hy- 1O ALEX MAZEL, P i E i dantoin.

9. 3 (3-chloromercuri-2-met11oxypr0py1)-1-methy1-hy- NICHOLAS RIZZO Examiner dantoin. A. D. ROLL-INS, Assistant Examiner. 

1. A 3 - MERCURI - 2 - OXYPROPYL - HYDANTOIN COMPOUND WHEREIN A DIVALENT MERCURY ATOM LINKS A PHARMACEUTICALLY ACCEPTABLE ANION TO THE TERMINAL CARBON ATOM OF AN OXYPROPYL GROUP AND THE REMAINING OXY VALENCE IS SATISFIED BY AN ALKYL, HYDROXYALKYL, OR HALOALKYL GROUP CONTAINING FROM ONE TO SIX CARBON ATOMS AND ANY SUBSTITUENTS PRESENT ON THE HYDANTOIN NUCLEUS ARE SELECTED FROM THE GROUP CONSISTING OF LOWER-ALKYL, MONOCYCLIC-ARYL-LOWER-ALKYL, MONOCYCLICARYL, OR MONOCYCLIC ARALKYL. 